Obesity is currently one of the major public health problems in the United States. Over 65% of the U.S. adult population is overweight. Obesity puts individuals at considerable risk for many disorders, such as heart disease, hypertension, diabetes, stroke, and certain types of cancer. Although there are a number of complex factors contributing to this trend, such as genetic predisposition, inactivity, lifestyle changes, and economic factors, the abundance and over consumption of calorically dense foods such as fats and sweets is largely responsible. Ingestion of food is required for survival, yet overabundance of energy-dense food has led to conditions that actually threaten survival. In the past decade, specific brain and peripheral systems involved in appetite control, particularly within the hypothalamus, have been discovered and characterized. However, relatively little is known about how brain networks involved in emotional regulation, executive function, and conscious control of behavior interact with hypothalamic energy balance-sensing systems. This would seem an important area of obesity research, as cognitive control, decision-making, and modulation of emotional responses in relation to the desire to eat are major determinants for the control of appetite in humans. Our work focuses on the role of the nucleus accumbens, a region within the ventral striatum, in the control of food motivation and food reward. We have shown that two main systems, one governed by endogenous opioid peptides and one by amino acid (GABA and glutamate) receptors, control certain aspects of ingestive behavior via connections with the lateral hypothalamus and other forebrain and brainstem regions. We aim to expand these investigations to study how cortical systems (i.e. the amygdala, gustatory cortex and prefrontal cortex) interact with ventral striatum and hypothalamus in the regulation of ingestive behavior. We will employ behavioral, pharmacological, neuroanatomical and molecular methodologies to address this question within an integrated, interdisciplinary framework.